Melissa Spencer* – Molecular Biology Institute

Publications:

Emami MR, Brimble MA, Espinoza A, Owens J, Whiteley LO, Casinghino S, Lanz TA, Farahat PK, Pellegrini M, Young CS, Thomas PG, McNally EM, Villalta SA, Schattgen SA, Spencer MJ. Single cell and TCR analysis of immune cells from AAV gene therapy-dosed Duchenne muscular dystrophy patients. Mol Ther Methods Clin Dev. 2024 Dec 12; 32(4):101349. view on PubMed

Mohan S, McNulty S, Thaxton C, Elnagheeb M, Owens E, Flowers M, Nunnery T, Self A, Palus B, Gorokhova S, Kennedy A, Niu Z, Johari M, Maiga AB, Macalalad K, Clause AR, Beckmann JS, Bronicki L, Cooper ST, Ganesh VS, Kang PB, Kesari A, Lek M, Levy J, Rufibach L, Savarese M, Spencer MJ, Straub V, Tasca G, Weihl CC. Expert panel curation of 31 genes in relation to limb girdle muscular dystrophy. Ann Clin Transl Neurol. 2024 Sep; 11(9):2268-2276. view on PubMed

Mohan S, McNulty S, Thaxton C, Elnagheeb M, Owens E, Flowers M, Nunnery T, Self A, Palus B, Gorokhova S, Kennedy A, Niu Z, Johari M, Maiga AB, Macalalad K, Clause AR, Beckmann JS, Bronicki L, Cooper ST, Ganesh VS, Kang PB, Kesari A, Lek M, Levy J, Rufibach L, Savarese M, Spencer MJ, Straub V, Tasca G, Weihl CC. Expert Panel Curation of 31 Genes in Relation to Limb Girdle Muscular Dystrophy. bioRxiv. 2024 May 06. view on PubMed

O'Brien JG, Willis AB, Long AM, Kwon J, Lee G, Li FW, Page PG, Vo AH, Hadhazy M, Spencer MJ, Crosbie RH, Demonbreun AR, McNally EM. The super-healing MRL strain promotes muscle growth in muscular dystrophy through a regenerative extracellular matrix. JCI Insight. 2024 Jan 04; 9(3). view on PubMed

Kohn DB, Chen YY, Spencer MJ. Successes and challenges in clinical gene therapy. Gene Ther. 2023 11; 30(10-11):738-746. view on PubMed

Hicks MR, Liu X, Young CS, Saleh K, Ji Y, Jiang J, Emami MR, Mokhonova E, Spencer MJ, Meng H, Pyle AD. Nanoparticles systemically biodistribute to regenerating skeletal muscle in DMD. J Nanobiotechnology. 2023 Aug 29; 21(1):303. view on PubMed

Coulis G, Jaime D, Guerrero-Juarez C, Kastenschmidt JM, Farahat PK, Nguyen Q, Pervolarakis N, McLinden K, Thurlow L, Movahedi S, Hughes BS, Duarte J, Sorn A, Montoya E, Mozaffar I, Dragan M, Othy S, Joshi T, Hans CP, Kimonis V, MacLean AL, Nie Q, Wallace LM, Harper SQ, Mozaffar T, Hogarth MW, Bhattacharya S, Jaiswal JK, Golann DR, Su Q, Kessenbrock K, Stec M, Spencer MJ, Zamudio JR, Villalta SA. Single-cell and spatial transcriptomics identify a macrophage population associated with skeletal muscle fibrosis. Sci Adv. 2023 07 07; 9(27):eadd9984. view on PubMed

Emami MR, Espinoza A, Young CS, Ma F, Farahat PK, Felgner PL, Chamberlain JS, Xu X, Pyle AD, Pellegrini M, Villalta SA, Spencer MJ. Innate and adaptive AAV-mediated immune responses in a mouse model of Duchenne muscular dystrophy. Mol Ther Methods Clin Dev. 2023 Sep 14; 30:90-102. view on PubMed

Coulis G, Jaime D, Guerrero-Juarez C, Kastenschmidt JM, Farahat PK, Nguyen Q, Pervolarakis N, McLinden K, Thurlow L, Movahedi S, Duarte J, Sorn A, Montoya E, Mozaffar I, Dragan M, Othy S, Joshi T, Hans CP, Kimonis V, MacLean AL, Nie Q, Wallace LM, Harper SQ, Mozaffar T, Hogarth MW, Bhattacharya S, Jaiswal JK, Golann DR, Su Q, Kessenbrock K, Stec M, Spencer MJ, Zamudio JR, Villalta SA. Single-cell and spatial transcriptomics identify a macrophage population associated with skeletal muscle fibrosis. bioRxiv. 2023 Apr 18. view on PubMed

Ligon JA, Sundby RT, Wedekind MF, Arnaldez FI, Del Rivero J, Wiener L, Srinivasan R, Spencer M, Carbonell A, Lei H, Shern J, Steinberg SM, Figg WD, Peer CJ, Zimmerman S, Moraly J, Xu X, Fox S, Chan K, Barbato MI, Andresson T, Taylor N, Pacak K, Killian JK, Dombi E, Linehan WM, Miettinen M, Piekarz R, Helman LJ, Meltzer P, Widemann B, Glod J. A Phase II Trial of Guadecitabine in Children and Adults with SDH-Deficient GIST, Pheochromocytoma, Paraganglioma, and HLRCC-Associated Renal Cell Carcinoma. Clin Cancer Res. 2023 01 17; 29(2):341-348. view on PubMed

Saleh KK, Xi H, Switzler C, Skuratovsky E, Romero MA, Chien P, Gibbs D, Gane L, Hicks MR, Spencer MJ, Pyle AD. Single cell sequencing maps skeletal muscle cellular diversity as disease severity increases in dystrophic mouse models. iScience. 2022 Nov 18; 25(11):105415. view on PubMed

Dowling JJ, Weihl CC, Spencer MJ. Molecular and cellular basis of genetically inherited skeletal muscle disorders. Nat Rev Mol Cell Biol. 2021 11; 22(11):713-732. view on PubMed

Liu J, Campagna J, John V, Damoiseaux R, Mokhonova E, Becerra D, Meng H, McNally EM, Pyle AD, Kramerova I, Spencer MJ. A Small-Molecule Approach to Restore a Slow-Oxidative Phenotype and Defective CaMKIIβ Signaling in Limb Girdle Muscular Dystrophy. Cell Rep Med. 2020 10 20; 1(7):100122. view on PubMed

Sengupta K, Mishra MK, Loro E, Spencer MJ, Pyle AD, Khurana TS. Genome Editing-Mediated Utrophin Upregulation in Duchenne Muscular Dystrophy Stem Cells. Mol Ther Nucleic Acids. 2020 Dec 04; 22:500-509. view on PubMed

Kramerova I, Marinov M, Owens J, Lee SJ, Becerra D, Spencer MJ. Myostatin inhibition promotes fast fibre hypertrophy but causes loss of AMP-activated protein kinase signalling and poor exercise tolerance in a model of limb-girdle muscular dystrophy R1/2A. J Physiol. 2020 09; 598(18):3927-3939. view on PubMed

Xi H, Langerman J, Sabri S, Chien P, Young CS, Younesi S, Hicks M, Gonzalez K, Fujiwara W, Marzi J, Liebscher S, Spencer M, Van Handel B, Evseenko D, Schenke-Layland K, Plath K, Pyle AD. A Human Skeletal Muscle Atlas Identifies the Trajectories of Stem and Progenitor Cells across Development and from Human Pluripotent Stem Cells. Cell Stem Cell. 2020 Jul 02; 27(1):181-185. view on PubMed

Kramerova I, Kumagai-Cresse C, Ermolova N, Mokhonova E, Marinov M, Capote J, Becerra D, Quattrocelli M, Crosbie RH, Welch E, McNally EM, Spencer MJ. Spp1 (osteopontin) promotes TGFβ processing in fibroblasts of dystrophin-deficient muscles through matrix metalloproteinases. Hum Mol Genet. 2019 10 15; 28(20):3431-3442. view on PubMed

Young CS, Pyle AD, Spencer MJ. CRISPR for Neuromuscular Disorders: Gene Editing and Beyond. Physiology (Bethesda). 2019 09 01; 34(5):341-353. view on PubMed

Malik R, Meng H, Wongkongkathep P, Corrales CI, Sepanj N, Atlasi RS, Klärner FG, Schrader T, Spencer MJ, Loo JA, Wiedau M, Bitan G. The molecular tweezer CLR01 inhibits aberrant superoxide dismutase 1 (SOD1) self-assembly in vitro and in the G93A-SOD1 mouse model of ALS. J Biol Chem. 2019 03 08; 294(10):3501-3513. view on PubMed

Ji Y, Liu X, Huang M, Jiang J, Liao YP, Liu Q, Chang CH, Liao H, Lu J, Wang X, Spencer MJ, Meng H. Development of self-assembled multi-arm polyrotaxanes nanocarriers for systemic plasmid delivery in vivo. Biomaterials. 2019 02; 192:416-428. view on PubMed

Kramerova I, Torres JA, Eskin A, Nelson SF, Spencer MJ. Calpain 3 and CaMKIIβ signaling are required to induce HSP70 necessary for adaptive muscle growth after atrophy. Hum Mol Genet. 2018 05 01; 27(9):1642-1653. view on PubMed

Wang DW, Mokhonova EI, Kendall GC, Becerra D, Naeini YB, Cantor RM, Spencer MJ, Nelson SF, Miceli MC. Repurposing Dantrolene for Long-Term Combination Therapy to Potentiate Antisense-Mediated DMD Exon Skipping in the mdx Mouse. Mol Ther Nucleic Acids. 2018 Jun 01; 11:180-191. view on PubMed

Gordish-Dressman H, Willmann R, Dalle Pazze L, Kreibich A, van Putten M, Heydemann A, Bogdanik L, Lutz C, Davies K, Demonbreun AR, Duan D, Elsey D, Fukada SI, Girgenrath M, Patrick Gonzalez J, Grounds MD, Nichols A, Partridge T, Passini M, Sanarica F, Schnell FJ, Wells DJ, Yokota T, Young CS, Zhong Z, Spurney C, Spencer M, De Luca A, Nagaraju K, Aartsma-Rus A. "Of Mice and Measures": A Project to Improve How We Advance Duchenne Muscular Dystrophy Therapies to the Clinic. J Neuromuscul Dis. 2018; 5(4):407-417. view on PubMed

Hicks MR, Hiserodt J, Paras K, Fujiwara W, Eskin A, Jan M, Xi H, Young CS, Evseenko D, Nelson SF, Spencer MJ, Handel BV, Pyle AD. ERBB3 and NGFR mark a distinct skeletal muscle progenitor cell in human development and hPSCs. Nat Cell Biol. 2018 01; 20(1):46-57. view on PubMed

Quattrocelli M, Capote J, Ohiri JC, Warner JL, Vo AH, Earley JU, Hadhazy M, Demonbreun AR, Spencer MJ, McNally EM. Genetic modifiers of muscular dystrophy act on sarcolemmal resealing and recovery from injury. PLoS Genet. 2017 Oct; 13(10):e1007070. view on PubMed

Yao J, Guihard PJ, Wu X, Blazquez-Medela AM, Spencer MJ, Jumabay M, Tontonoz P, Fogelman AM, Boström KI, Yao Y. Vascular endothelium plays a key role in directing pulmonary epithelial cell differentiation. J Cell Biol. 2017 10 02; 216(10):3369-3385. view on PubMed

Young CS, Mokhonova E, Quinonez M, Pyle AD, Spencer MJ. Creation of a Novel Humanized Dystrophic Mouse Model of Duchenne Muscular Dystrophy and Application of a CRISPR/Cas9 Gene Editing Therapy. J Neuromuscul Dis. 2017; 4(2):139-145. view on PubMed

Quattrocelli M, Spencer MJ, McNally EM. Outside in: The matrix as a modifier of muscular dystrophy. Biochim Biophys Acta Mol Cell Res. 2017 Mar; 1864(3):572-579. view on PubMed

Gibbs EM, Marshall JL, Ma E, Nguyen TM, Hong G, Lam JS, Spencer MJ, Crosbie-Watson RH. High levels of sarcospan are well tolerated and act as a sarcolemmal stabilizer to address skeletal muscle and pulmonary dysfunction in DMD. Hum Mol Genet. 2016 12 15; 25(24):5395-5406. view on PubMed

Capote J, Kramerova I, Martinez L, Vetrone S, Barton ER, Sweeney HL, Miceli MC, Spencer MJ. Osteopontin ablation ameliorates muscular dystrophy by shifting macrophages to a pro-regenerative phenotype. J Cell Biol. 2016 04 25; 213(2):275-88. view on PubMed

Kramerova I, Ermolova N, Eskin A, Hevener A, Quehenberger O, Armando AM, Haller R, Romain N, Nelson SF, Spencer MJ. Failure to up-regulate transcription of genes necessary for muscle adaptation underlies limb girdle muscular dystrophy 2A (calpainopathy). Hum Mol Genet. 2016 06 01; 25(11):2194-2207. view on PubMed

DiFranco M, Kramerova I, Vergara JL, Spencer MJ. Attenuated Ca(2+) release in a mouse model of limb girdle muscular dystrophy 2A. Skelet Muscle. 2016; 6:11. view on PubMed

Young CS, Hicks MR, Ermolova NV, Nakano H, Jan M, Younesi S, Karumbayaram S, Kumagai-Cresse C, Wang D, Zack JA, Kohn DB, Nakano A, Nelson SF, Miceli MC, Spencer MJ, Pyle AD. A Single CRISPR-Cas9 Deletion Strategy that Targets the Majority of DMD Patients Restores Dystrophin Function in hiPSC-Derived Muscle Cells. Cell Stem Cell. 2016 Apr 07; 18(4):533-40. view on PubMed

Martinez L, Ermolova NV, Ishikawa TO, Stout DB, Herschman HR, Spencer MJ. A reporter mouse for optical imaging of inflammation in mdx muscles. Skelet Muscle. 2015; 5:15. view on PubMed

Mokhonova EI, Avliyakulov NK, Kramerova I, Kudryashova E, Haykinson MJ, Spencer MJ. The E3 ubiquitin ligase TRIM32 regulates myoblast proliferation by controlling turnover of NDRG2. Hum Mol Genet. 2015 May 15; 24(10):2873-83. view on PubMed

Ermolova N, Kramerova I, Spencer MJ. Autolytic activation of calpain 3 proteinase is facilitated by calmodulin protein. J Biol Chem. 2015 Jan 09; 290(2):996-1004. view on PubMed

Villalta SA, Rosenthal W, Martinez L, Kaur A, Sparwasser T, Tidball JG, Margeta M, Spencer MJ, Bluestone JA. Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy. Sci Transl Med. 2014 Oct 15; 6(258):258ra142. view on PubMed

Kendall GC, Mokhonova EI, Moran M, Sejbuk NE, Wang DW, Silva O, Wang RT, Martinez L, Lu QL, Damoiseaux R, Spencer MJ, Nelson SF, Miceli MC. Dantrolene enhances antisense-mediated exon skipping in human and mouse models of Duchenne muscular dystrophy. Sci Transl Med. 2012 Dec 12; 4(164):164ra160. view on PubMed

Chao LC, Wroblewski K, Ilkayeva OR, Stevens RD, Bain J, Meyer GA, Schenk S, Martinez L, Vergnes L, Narkar VA, Drew BG, Hong C, Boyadjian R, Hevener AL, Evans RM, Reue K, Spencer MJ, Newgard CB, Tontonoz P. Skeletal muscle Nur77 expression enhances oxidative metabolism and substrate utilization. J Lipid Res. 2012 Dec; 53(12):2610-9. view on PubMed

Jaka O, Kramerova I, Azpitarte M, López de Munain A, Spencer M, Sáenz A. C3KO mouse expression analysis: downregulation of the muscular dystrophy Ky protein and alterations in muscle aging. Neurogenetics. 2012 Nov; 13(4):347-57. view on PubMed

Kudryashova E, Kramerova I, Spencer MJ. Satellite cell senescence underlies myopathy in a mouse model of limb-girdle muscular dystrophy 2H. J Clin Invest. 2012 May; 122(5):1764-76. view on PubMed

Kudryashova E, Struyk A, Mokhonova E, Cannon SC, Spencer MJ. The common missense mutation D489N in TRIM32 causing limb girdle muscular dystrophy 2H leads to loss of the mutated protein in knock-in mice resulting in a Trim32-null phenotype. Hum Mol Genet. 2011 Oct 15; 20(20):3925-32. view on PubMed

Ermolova N, Kudryashova E, DiFranco M, Vergara J, Kramerova I, Spencer MJ. Pathogenity of some limb girdle muscular dystrophy mutations can result from reduced anchorage to myofibrils and altered stability of calpain 3. Hum Mol Genet. 2011 Sep 01; 20(17):3331-45. view on PubMed

Kim MH, Kay DI, Rudra RT, Chen BM, Hsu N, Izumiya Y, Martinez L, Spencer MJ, Walsh K, Grinnell AD, Crosbie RH. Myogenic Akt signaling attenuates muscular degeneration, promotes myofiber regeneration and improves muscle function in dystrophin-deficient mdx mice. Hum Mol Genet. 2011 Apr 01; 20(7):1324-38. view on PubMed

Shieh PB, Kudryashova E, Spencer MJ. Limb-girdle muscular dystrophy 2H and the role of TRIM32. Handb Clin Neurol. 2011; 101:125-33. view on PubMed

Nelson SF, Crosbie RH, Miceli MC, Spencer MJ. Emerging genetic therapies to treat Duchenne muscular dystrophy. Curr Opin Neurol. 2009 Oct; 22(5):532-8. view on PubMed

Mellgren RL, Miyake K, Kramerova I, Spencer MJ, Bourg N, Bartoli M, Richard I, Greer PA, McNeil PL. Calcium-dependent plasma membrane repair requires m- or mu-calpain, but not calpain-3, the proteasome, or caspases. Biochim Biophys Acta. 2009 Dec; 1793(12):1886-93. view on PubMed

Kramerova I, Kudryashova E, Wu B, Germain S, Vandenborne K, Romain N, Haller RG, Verity MA, Spencer MJ. Mitochondrial abnormalities, energy deficit and oxidative stress are features of calpain 3 deficiency in skeletal muscle. Hum Mol Genet. 2009 Sep 01; 18(17):3194-205. view on PubMed

Vetrone SA, Montecino-Rodriguez E, Kudryashova E, Kramerova I, Hoffman EP, Liu SD, Miceli MC, Spencer MJ. Osteopontin promotes fibrosis in dystrophic mouse muscle by modulating immune cell subsets and intramuscular TGF-beta. J Clin Invest. 2009 Jun; 119(6):1583-94. view on PubMed

Kudryashova E, Wu J, Havton LA, Spencer MJ. Deficiency of the E3 ubiquitin ligase TRIM32 in mice leads to a myopathy with a neurogenic component. Hum Mol Genet. 2009 Apr 01; 18(7):1353-67. view on PubMed

Beckmann JS, Spencer M. Calpain 3, the "gatekeeper" of proper sarcomere assembly, turnover and maintenance. Neuromuscul Disord. 2008 Dec; 18(12):913-21. view on PubMed

Kramerova I, Kudryashova E, Wu B, Ottenheijm C, Granzier H, Spencer MJ. Novel role of calpain-3 in the triad-associated protein complex regulating calcium release in skeletal muscle. Hum Mol Genet. 2008 Nov 01; 17(21):3271-80. view on PubMed

Groshong JS, Spencer MJ, Bhattacharyya BJ, Kudryashova E, Vohra BP, Zayas R, Wollmann RL, Miller RJ, Gomez CM. Calpain activation impairs neuromuscular transmission in a mouse model of the slow-channel myasthenic syndrome. J Clin Invest. 2007 Oct; 117(10):2903-12. view on PubMed

Cohen N, Kudryashova E, Kramerova I, Anderson LV, Beckmann JS, Bushby K, Spencer MJ. Identification of putative in vivo substrates of calpain 3 by comparative proteomics of overexpressing transgenic and nontransgenic mice. Proteomics. 2006 Nov; 6(22):6075-84. view on PubMed

Kramerova I, Kudryashova E, Wu B, Spencer MJ. Regulation of the M-cadherin-beta-catenin complex by calpain 3 during terminal stages of myogenic differentiation. Mol Cell Biol. 2006 Nov; 26(22):8437-47. view on PubMed

Kramerova I, Beckmann JS, Spencer MJ. Molecular and cellular basis of calpainopathy (limb girdle muscular dystrophy type 2A). Biochim Biophys Acta. 2007 Feb; 1772(2):128-44. view on PubMed

Nazarian R, Starcevic M, Spencer MJ, Dell'Angelica EC. Reinvestigation of the dysbindin subunit of BLOC-1 (biogenesis of lysosome-related organelles complex-1) as a dystrobrevin-binding protein. Biochem J. 2006 May 01; 395(3):587-98. view on PubMed

Kudryashova E, Kudryashov D, Kramerova I, Spencer MJ. Trim32 is a ubiquitin ligase mutated in limb girdle muscular dystrophy type 2H that binds to skeletal muscle myosin and ubiquitinates actin. J Mol Biol. 2005 Nov 25; 354(2):413-24. view on PubMed

Huebsch KA, Kudryashova E, Wooley CM, Sher RB, Seburn KL, Spencer MJ, Cox GA. Mdm muscular dystrophy: interactions with calpain 3 and a novel functional role for titin's N2A domain. Hum Mol Genet. 2005 Oct 01; 14(19):2801-11. view on PubMed

Kramerova I, Kudryashova E, Venkatraman G, Spencer MJ. Calpain 3 participates in sarcomere remodeling by acting upstream of the ubiquitin-proteasome pathway. Hum Mol Genet. 2005 Aug 01; 14(15):2125-34. view on PubMed

Kramerova I, Kudryashova E, Tidball JG, Spencer MJ. Null mutation of calpain 3 (p94) in mice causes abnormal sarcomere formation in vivo and in vitro. Hum Mol Genet. 2004 Jul 01; 13(13):1373-88. view on PubMed

Guyon JR, Kudryashova E, Potts A, Dalkilic I, Brosius MA, Thompson TG, Beckmann JS, Kunkel LM, Spencer MJ. Calpain 3 cleaves filamin C and regulates its ability to interact with gamma- and delta-sarcoglycans. Muscle Nerve. 2003 Oct; 28(4):472-83. view on PubMed

Gosselin LE, Barkley JE, Spencer MJ, McCormick KM, Farkas GA. Ventilatory dysfunction in mdx mice: impact of tumor necrosis factor-alpha deletion. Muscle Nerve. 2003 Sep; 28(3):336-43. view on PubMed

Tidball JG, Spencer MJ. Skipping to new gene therapies for muscular dystrophy. Nat Med. 2003 Aug; 9(8):997-8. view on PubMed

Hodgetts SI, Spencer MJ, Grounds MD. A role for natural killer cells in the rapid death of cultured donor myoblasts after transplantation. Transplantation. 2003 Mar 27; 75(6):863-71. view on PubMed

Tidball JG, Spencer MJ. Expression of a calpastatin transgene slows muscle wasting and obviates changes in myosin isoform expression during murine muscle disuse. J Physiol. 2002 12 15; 545(3):819-28. view on PubMed

Spencer MJ, Mellgren RL. Overexpression of a calpastatin transgene in mdx muscle reduces dystrophic pathology. Hum Mol Genet. 2002 Oct 01; 11(21):2645-55. view on PubMed

Spencer MJ, Guyon JR, Sorimachi H, Potts A, Richard I, Herasse M, Chamberlain J, Dalkilic I, Kunkel LM, Beckmann JS. Stable expression of calpain 3 from a muscle transgene in vivo: immature muscle in transgenic mice suggests a role for calpain 3 in muscle maturation. Proc Natl Acad Sci U S A. 2002 Jun 25; 99(13):8874-9. view on PubMed

Taveau M, Stockholm D, Spencer M, Richard I. Quantification of splice variants using molecular beacon or scorpion primers. Anal Biochem. 2002 Jun 15; 305(2):227-35. view on PubMed

Spencer MJ, Tidball JG. Do immune cells promote the pathology of dystrophin-deficient myopathies? Neuromuscul Disord. 2001 Sep; 11(6-7):556-64. view on PubMed

Spencer MJ, Marino MW, Winckler WM. Altered pathological progression of diaphragm and quadriceps muscle in TNF-deficient, dystrophin-deficient mice. Neuromuscul Disord. 2000 Dec; 10(8):612-9. view on PubMed

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